Sarcoglycan subcomplex in normal human smooth muscle: An immunohistochemical and molecular study

The sarcoglycans are transmembrane components of the dystrophin-glycoprotein complex, which links the cytoskeleton to the extracellular matrix in adult muscle fibers. Sarcoglycans seem to be functionally and pathologically as important as dystrophin. In the skeletal and cardiac muscle, the sarcoglycan subcomplex is a heterotetrameric unit composed of the transmembrane glycoproteins α-, β-, γ- and δ-sarcoglycan. A fifth sarcoglycan with significant homology to α-sarcoglycan, ε-sarcoglycan, has been identified; this sarcoglycan is expressed in both muscle and non-muscle cells. It is hypothesized that ε-sarcoglycan might replace α-sarcoglycan in smooth muscle, forming a novel sarcoglycan subcomplex consisting of ε-, β-, γ-, and δ-sarcoglycan. Recently, ζ-sarcoglycan, a novel sarcoglycan highly related to γ-sarcoglycan and δ-sarcoglycan, has been identified. On this basis, growing evidence suggests that there are two types of sarcoglycan complex; one, in skeletal and cardiac muscle, consisting of α-, β-, γ- and δ-sarcoglycan; and the other, in smooth muscle, containing β-, δ-, ζ- and ε-sarcoglycan. ε-sarcoglycan may be substituted for α-sarcoglycan in a subset of striated muscle complexes. Our results, obtained with immunofluorescence semi-quantitative analysis and molecular methods on smooth muscle biopsies of human adult gastroenteric tract, show for the first time that α-sarcoglycan fluorescence is also always detectable in smooth muscle, although its staining pattern is lower than ε-sarcoglycan. Normal α-sarcoglycan staining was detected at times, whereas there was reduced, but clearly detectable staining for ε-sarcoglycan. Moreover, γ-sarcoglycan staining is always detectable in all analyzed biopsies. On the basis of our results, we would be able to hypothesize the existence of a pentameric or, considering ζ-sarcolgycan, a hexameric arrangement of the sarcoglycan subcomplex. The hexameric sarcoglycan subcomplex, in conformity with a larger or lower expression of single sarcoglycans, could characterize skeletal, cardiac or smooth muscle, or distinct parts of gastroenteric tract. It is intriguing to integrate these results with other vascular and urogenital smooth muscle, skeletal and cardiac muscle, while also analyzing ζ-sarcoglycan.